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Introduction
Systemic lupus erythematosus (SLE) is an autoimmune disease involving multiple organ systems. Previous studies have suggested that interferon-lambda 1 (IFN-λ1), a type III interferon, plays an immunomodulatory role. In this study we investigated its role in SLE, including its correlation with disease activity, organ disorder and production of chemokines. 相似文献24.
Cristina Firanescu Paul NM Lohle Jolanda de Vries Caroline A Klazen Job R Juttmann William Clark Willem Jan van Rooij 《Trials》2011,12(1):1-5
Background
Combination of erlotinib and bevacizumab is a promising regimen in advanced non-squamous non-small-cell lung cancer (NSCLC). We are conducting a single arm phase II trial which aims to evaluate the efficacy and safety of this regime as a second- or third-line chemotherapy.Methods
Key eligibility criteria were histologically or cytologically confirmed non-squamous NSCLC, stage III/IV or recurrent NSCLC not indicated radical chemoradiation, prior one or two regimen of chemotherapy, age 20 years or more, and performance status of two or less. The primary endpoint is objective response rate. The secondary endpoints include overall survival, progression-free survival, disease control rate and incidence of adverse events. This trial plans to accrue 80 patients based on a two-stage design employing a binomial distribution with an alternative hypothesis response rate of 35% and a null hypothesis threshold response rate of 20%. A subset analysis according to EGFR mutation status is planned.Discussion
We have presented the design of a single arm phase II trial to evaluate the efficacy and safety of combination of bevacizumab and erlotinib in advanced non-squamous NSCLC patients. In particular we are interested in determining the merit of further development of this regimen and whether prospective patient selection using EGFR gene is necessary in future trials.Trial registration
This trial was registered at the UMIN Clinical Trials Registry as UMIN000004255 (http://www.umin.ac.jp/ctr/index.htm). 相似文献25.
J. Romiguier J. Lourenco P. Gayral N. Faivre L. A. Weinert S. Ravel M. Ballenghien V. Cahais A. Bernard E. Loire L. Keller N. Galtier 《Journal of evolutionary biology》2014,27(3):593-603
The evolution of reproductive division of labour and social life in social insects has lead to the emergence of several life‐history traits and adaptations typical of larger organisms: social insect colonies can reach masses of several kilograms, they start reproducing only when they are several years old, and can live for decades. These features and the monopolization of reproduction by only one or few individuals in a colony should affect molecular evolution by reducing the effective population size. We tested this prediction by analysing genome‐wide patterns of coding sequence polymorphism and divergence in eusocial vs. noneusocial insects based on newly generated RNA‐seq data. We report very low amounts of genetic polymorphism and an elevated ratio of nonsynonymous to synonymous changes – a marker of the effective population size – in four distinct species of eusocial insects, which were more similar to vertebrates than to solitary insects regarding molecular evolutionary processes. Moreover, the ratio of nonsynonymous to synonymous substitutions was positively correlated with the level of social complexity across ant species. These results are fully consistent with the hypothesis of a reduced effective population size and an increased genetic load in eusocial insects, indicating that the evolution of social life has important consequences at both the genomic and population levels. 相似文献
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Tania Lourenco Robert Pickard Luke Vale Adrian Grant Cynthia Fraser Graeme MacLennan James N’Dow 《BMJ (Clinical research ed.)》2008,337(7660):36-39
Objective To compare the effectiveness and risk profile of newer methods for endoscopic ablation of the prostate against the current standard of transurethral resection.Design Systematic review and meta-analysis.Data sources Electronic and paper records in subject area up to March 2006.Review methods We searched for randomised controlled trials of endoscopic ablative interventions that included transurethral resection of prostate as one of the treatment arms. Two reviewers independently extracted data and assessed quality. Meta-analyses of prespecified outcomes were done using fixed and random effects models and reported using relative risk or weighted mean difference.Results We identified 45 randomised controlled trials meeting the inclusion criteria and reporting on 3970 participants. The reports were of moderate to poor quality, with small sample sizes. None of the newer technologies resulted in significantly greater improvement in symptoms than transurethral resection at 12 months, although a trend suggested a better outcome with holmium laser enucleation (random effects weighted mean difference −0.82, 95% confidence interval 1.76 to 0.12) and worse outcome with laser vaporisation (1.49, −0.40 to 3.39). Improvements in secondary measures, such as peak urine flow rate, were consistent with change in symptoms. Blood transfusion rates were higher for transurethral resection than for the newer methods (4.8% v 0.7%) and men undergoing laser vaporisation or diathermy vaporisation were more likely to experience urinary retention (6.7% v 2.3% and 3.6% v 1.1%). Hospital stay was up to one day shorter for the newer technologies.Conclusions Although men undergoing more modern methods of removing benign prostatic enlargement have similar outcomes to standard transurethral resection of prostate along with fewer requirements for blood transfusion and shorter hospital stay, the quality of current evidence is poor. The lack of any clearly more effective procedure suggests that transurethral resection should remain the standard approach. 相似文献
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Afforestation is a recommended practice to mitigate global warming. However, their implementation may generate undesirable impacts, mostly if exotic species are used. Plantations of Pinus radiata D Don in Ventania (Bs. As., Argentina) soils showed notorious increments of extractable P (Pe), which could affect the dynamic of this element as well as the degree of phosphorus saturation (GSPBray). The objectives of this study were: i) to quantify the GSPBray in Mollisols afforested with P. radiata comparing the results with those coming from adjacent, natural grassland areas (base line); ii) to evaluate the potential environmental risk induced by afforestation through the identification of a change point (PC) in the GSPBray indicative of a phosphate leaching increment. Treatments included mature stands of P. radiata (TB) and adjacent areas with natural grassland vegetation (TP). Samples were taken at 0-15; 15-30 and 30-45 cm soil depth, and texture, pH, total organic carbon (COT), Pe, soluble reactive phosphorus (PSR), phosphorus sorption index (ISP) and GSPBray were determined. The results showed a significant acidification in TB and an increase in the COT stock, indicating an additional atmospheric CO2 sequestration by the trees. The Pe and PSR values were notoriously higher in TB, and they were reflected in a significant increment in the GSPBray with respect to TP. The detection of a significant PC in the GSPBray-PSR regression indicates higher chances of phosphate leaching in the forest stands, which could reach water courses, lakes and artificial reservoirs promoting their eutrophication. Because of the potential environmental pollution risk of biologic origin derived from the afforestation with P. radiata in Mollisols areas, their inclusion in clean development practices must be reconsidered. 相似文献
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Dingcheng Gao Vivek Mittal Yi Ban Ana Rita Lourenco Shira Yomtoubian Sharrell Lee 《生物学前沿》2018,13(4):277-286
Background
Metastasis is the primary cause of mortality in cancer patients. Therefore, elucidating the genetics and epigenetics of metastatic tumor cells and the mechanisms by which tumor cells acquire metastatic properties constitute significant challenges in cancer research.Objective
To summarize the current understandings of the specific genotype and phenotype of the metastatic tumor cells.Method and Result
In-depth genetic analysis of tumor cells, especially with advances in the next-generation sequencing, have revealed insights of the genotypes of metastatic tumor cells. Also, studies have shown that the cancer stem cell (CSC) and epithelial to mesenchymal transition (EMT) phenotypes are associated with the metastatic cascade.Conclusion
In this review, we will discuss recent advances in the field by focusing on the genomic instability and phenotypic dynamics of metastatic tumor cells.29.
Philipp Mergenthaler Santosh Hariharan James M. Pemberton Corey Lourenco Linda Z. Penn David W. Andrews 《PLoS computational biology》2021,17(2)
Phenotypic profiling of large three-dimensional microscopy data sets has not been widely adopted due to the challenges posed by cell segmentation and feature selection. The computational demands of automated processing further limit analysis of hard-to-segment images such as of neurons and organoids. Here we describe a comprehensive shallow-learning framework for automated quantitative phenotyping of three-dimensional (3D) image data using unsupervised data-driven voxel-based feature learning, which enables computationally facile classification, clustering and advanced data visualization. We demonstrate the analysis potential on complex 3D images by investigating the phenotypic alterations of: neurons in response to apoptosis-inducing treatments and morphogenesis for oncogene-expressing human mammary gland acinar organoids. Our novel implementation of image analysis algorithms called Phindr3D allowed rapid implementation of data-driven voxel-based feature learning into 3D high content analysis (HCA) operations and constitutes a major practical advance as the computed assignments represent the biology while preserving the heterogeneity of the underlying data. Phindr3D is provided as Matlab code and as a stand-alone program (https://github.com/DWALab/Phindr3D). 相似文献
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D B Yeates C G Larkridge A Marrinelli R D Harshbarger R P Musselman B Pitt T N Raju T R Gerrity R V Lourenco 《Biorheology》1984,21(1-2):273-283
Measurements of the rate of mucociliary transport in the airways of the lower respiratory tract have been shown to be influenced by the techniques and protocols used. To avoid the effects associated with invasive techniques and anesthesia in animal models used to study the effect of maturation, drugs, disease, and inhaled pollutants on mucociliary transport we have developed unsedated dog and baboon models of mucociliary transport using radioaerosol techniques. As far as they have been tested these animal models of mucociliary transport react to drugs such as isoproterenol and atropine in the same manner as in man. 相似文献